Cited by 287Immunodeficiency and Autoimmune DisordersTuberculosis Research and EpidemiologyNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

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Bustamante, Jacinta, Arias, Andres A, Vogt, Guillaume, Picard, Capucine, Galicia, Lizbeth Blancas, Prando, Carolina, Grant, Audrey V, Marchal, Christophe C +22 more·2011·Nature Immunology

Abstract

Germline mutations in CYBB, the human gene encoding the gp91(phox) subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This 'experiment of nature' indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria.

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  • Mutations or polymorphisms in the human NOS2 or NOX2 genes are associated with an increased susceptibility to or a more severe course of tuberculosis.

    “It has also been observed that both mutations or polymorphisms in the humans NOS2 or NOX2 genes are associated with an increased susceptibility to or a more severe course of tuberculosis (74, 75).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [75]

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Research works printed but not linked: 3

  1. [22]Yu L Biosynthesis of flavocytochrome b558. gp91phox is synthesized as a 65-kDa precursor (p65) in the endoplasmic reticulum J Biol Chem 274 4364 4369 1999 9933639
  2. [24]Yu L Zhen L Dinauer MC Biosynthesis of the phagocyte NADPH oxidase cytochrome b558. Role of heme incorporation and heterodimer formation in maturation and stability of gp91phox and p22phox subunits J Biol Chem 272 27288 27294 1997 9341176
  3. [30]Burritt JB Phage display epitope mapping of human neutrophil flavocytochrome b558. Identification of two juxtaposed extracellular domains J Biol Chem 276 2053 2061 2001 11027685

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Authors
Bustamante, J., Arias, A. A., Vogt, G., Picard, C., Galicia, L. B., Prando, C., Grant, A. V., Marchal, C. C., Hubeau, M., Chapgier, A., de Beaucoudrey, L., Puel, A., Feinberg, J., Valinetz, E., Jannière, L., Besse, C., Boland, A., Brisseau, J.-M., Blanche, S., Lortholary, O., Fieschi, C., Emile, J.-F., Boisson-Dupuis, S., Al-Muhsen, S., Woda, B., Newburger, P. E., Condino-Neto, A., Dinauer, M. C., Abel, L., & Casanova, J.-L.
Affiliations
  • Inserm (FR)
  • Rockefeller University (US)
  • Indiana University Indianapolis (US)
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Hôpital Necker-Enfants Malades (FR)
  • University of Massachusetts Chan Medical School (US)
Corresponding author
Casanova, Jean-Laurent
Venue
Nature Immunology
Published
2011-01-30
Volume
12
Issue
3
Pages
213-221
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W1973241546
Cited by
287
References
52
Citations by year
2026: 7 · 2025: 6 · 2024: 15 · 2023: 14 · 2022: 17 · 2021: 22 · 2020: 16 · 2019: 29 · 2018: 17 · 2017: 11 · 2016: 16 · 2015: 13 · 2014: 28 · 2013: 32 · 2012: 27
FWCI
14.39
Type
journal article
Language
en
Open access
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repository University of Antioquia (University of Antioquia) (publishedVersion, cc-by)
  • Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • eScholarship@UMassChan (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • March of Dimes Foundation
  • Riley Children's Foundation
  • Agence Nationale de la Recherche
  • Institut National de la Santé et de la Recherche Médicale
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Institut Universitaire de France
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL045635, HL045635)
  • National Institute of Allergy and Infectious Diseases (R21AI079788, R01AI089970, AI079788, R37AI095983)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK054369, DK-54369)
  • National Center for Research Resources (UL1RR024143)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
CYBB, gp91phox, NADPH oxidase, X-linked chronic granulomatous disease, Mendelian susceptibility to mycobacterial disease, macrophages, respiratory burst, monocyte-derived macrophages, germline mutations, X-linked recessive inheritance
MeSH terms
NADPH Oxidase 2, Animals, Cricetulus, Cricetinae, Humans, Macrophages, Male, Membrane Glycoproteins, Mutation, Tuberculosis, CHO Cells, NADPH Oxidases, Genetic Predisposition to Disease, Genes, X-Linked

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